Chloroform

CAS RN: 67-66-3

Toxicity Summary

IDENTIFICATION AND USE: Chloroform is a clear, colorless liquid. It is used in the manufacture of fluorcarbon-22. Chloroform is a solvent for fats, oils, rubber, alkaloids, waxes, gutta-percha, resins. It is also used as cleansing agent, as well as in fire extinguishers to lower the freezing temperature of carbon tetrachloride, and in the rubber industry. Chloroform was formerly used as an anesthetic and in pharmaceutical preparation immediately prior to World War II. However, these uses have been banned. HUMAN STUDIES: In humans, anesthesia with chloroform may result in death due to respiratory and cardiac arrhythmias and failure. Renal tubular necrosis and renal dysfunction have also been observed in humans. Chloroform is irritating to mucous membranes, producing gastroenteritis with persistent nausea and vomiting. Symptoms following ingestion of chloroform are similar to those following inhalation. Cases of severe intoxication after suicidal attempts, with the same pattern of symptoms as after anesthetic use, have been reported. There are considerable inter-individual differences in susceptibility. Some persons presented serious illness after an oral dose of 7.5 g of chloroform, whereas others survived a dose of 270 g chloroform. Long term exposure to concentrations of 100-1,000 mg/cu m (20-200 ppm) of chloroform produce mainly neurological effects, with increased incidence of symptoms such as fatigue, nausea, vomiting, lassitude, dry mouth, and anorexia. Some studies also observed effects on the liver, including jaundice, increased serum enzyme levels, and increased liver size. Exposure to concentrated chloroform vapors causes a stinging sensation in the eye. Splashing of the liquid into the eye evokes burning, pain and redness of the conjunctival tissue. Occasional injury of the corneal epithelium will recover fully within a few days. Dermal contact with chloroform causes chemical dermatitis (symptoms: irritation, reddening, blistering and burns). Chloroform with metabolic activation failed to induce chromosome breakage or sister-chromatid exchanges in human lymphocytes. ANIMAL STUDIES: The oxidative biotransformation of chloroform is catalyzed by cytochrome P-450 to produce trichloromethanol. Loss of HCl from trichloromethanol produces phosgene as a reactive intermediate. The reaction of phosgene with tissue proteins is associated with cell damage and death. The liver is the target organ for acute toxicity in rats and several strains of mice. Liver damage is characterized by early fatty infiltration and balloon cells, progressing to centrilobular necrosis and then massive necrosis. The kidney is the target organ in male mice of other more sensitive strains. The kidney damage starts with hydropic degeneration and progresses to necrosis of the proximal tubules. Mice are more sensitive to chloroform toxicity than rats. The carcinogenic effects of chloroform on the liver and kidney of rodents appear to be closely related to cytotoxic and cell replicative effects observed in the target organs. Chloroform has little, if any, capability to induce gene mutation or other types of direct damage to DNA. Two problems potentially compromise the interpretation of mutagenicity data on chloroform. First, there is a possibility that ethyl and diethylcarbonate, produced by reaction of phosgene with ethanol that is routinely added to U.S.P (US Pharmacopoeia) chloroform, could generate false positive results. Secondly, testing of chloroform must be done in a sealed system because of its volatility, and so studies that did not take this factor into account could give false negative results. There are some limited data to suggest that chloroform is toxic to the fetus but only at doses that are maternally toxic. ECOTOXICITY STUDIES: Levels of chloroform in surface waters are generally low and would not be expected to present a hazard to aquatic organisms. However, higher levels of chloroform in surface water resulting from industrial discharges or spills may be hazardous to the embryo-larval stages of some aquatic species.
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